Enantiopure Β-amino Research Articles

Spiroborate ester-mediated asymmetric synthesis of beta-hydroxy ethers and its conversion to highly enantiopure beta-amino ethers.

Borane-mediated reduction of aryl and alkyl ketones with alpha-aryl- and alpha-pyridyloxy groups affords beta-hydroxy ethers in high enantiomeric purity (up to 99% ee) and in good yield, using as catalyst 10 mol % of spiroborate ester 1 derived from (S)-diphenylprolinol. Representative beta-hydroxy ethers are successfully converted to beta-amino ethers, with minor epimerization, by phthalimide substitution under Mitsunobu's conditions followed by hydrazinolysis to obtain primary amino ethers or by imide reduction with borane to afford beta-2,3-dihydro-1H-isoindol ethers. Nonracemic Mexiletine and nAChR analogues with potential biological activity are also synthesized in excellent yield by mesylation of key beta-hydroxy pyridylethers and substitution with five-, six-, and seven-membered ring heterocyclic amines.

Arthrobacter sp. lipase immobilization for preparation of enantiopure masked β-amino alcohols

Recent reports on immobilization of lipase from Arthrobacter sp. (ABL, MTCC 5125; IIIM isolate) on insoluble polymers have shown altered properties including stability and enantioselectivity. Present work demonstrates a facile method for the preparation of enantiopure β-amino alcohols by modulation of ABL enzyme properties via immobilization on insoluble as well as soluble supports using entrapment/covalent binding techniques. Efficacies of immobilized ABL on insoluble supports prepared from tetraethylorthosilicate/aminopropyltriethoxy silane and soluble supports derived from copolymerization of N-vinyl pyrrolidone-allylglycidyl ether (ANP type)/ N-vinyl pyrrolidone-glycidyl methacrylate (GNP type) for kinetic resolution of masked β-amino alcohols have been studied vis-à-vis free ABL enzyme/wet cell biomass. The immobilized lipase on different insoluble/soluble supports has shown 21–110 mg/g protein binding and 30–700 U/g activity for hydrolyzing tributyrin substrate. The findings have shown a significant enhancement in enantioselectivity (ee 99%) vis-à-vis wet cell biomass providing ee 70–90% for resolution of β-amino alcohols.

Candida antarctica lipase B-catalyzed ring opening of 4-arylalkyl-substituted β-lactams

The Lipolase-catalyzed ring opening of racemic 4-benzyl- 3 and 4-phenylethyl-2-azetidinone 4 was performed with 0.5equiv of H2O in diisopropyl ether at 45°C. The resulting (S)-β-amino acid 5 or 6 (ee⩾87%) and (R)-β-lactam 7 or 8 (ee>99%) enantiomers could easily be separated. The ring opening of enantiomeric β-lactams with 18% aqueous HCl afforded the corresponding enantiopure β-amino acid hydrochlorides 9 and 10 (ee>99%).

New Chiral Hydroxyoxazolines Based on Ketopinic Acid and Their Use in the Asymmetric Diels-Alder Reaction

Several chiral hydroxyoxazolines have been prepared starting from (1 S)-(+)-ketopinic acid and enantiopure β-amino -alcohols by short synthetic routes. They have been employed in the catalytic asymmetric Diels-Alder reaction, resulting in ee values of up to 90%.

Biocatalysis as a Profound Tool in the Preparation of Highly Enantiopure β‐Amino Acids

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Preparation of Enantiopure β‐Amino Acids by Homologation of α‐Amino Acids

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Biocatalysis as a profound tool in the preparation of highly enantiopure β-amino acids

Enzymatic preparations of highly enantiopure β-amino acids have been reviewed. The report contains 212 references.

Synthesis of Enantiopure Azetidines: A Route to New β‐Amino Alcohols.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access the actual ChemInform Abstract, please click on HTML or PDF.

Enantioselective Hydrogenation of (E)‐ and (Z)‐Isomeric Ethyl 3‐Acetamidobutenoates with Rh‐Bisphosphine Complexes: Effects of Substrate Geometry and Solvents on Reaction Rates and Catalyst Reusability.

Enantiopure β-amino acids are crucial structural features of numerous biologically active natural products as well as important building blocks for the synthesis of β-peptides and β-lactam antibiotics. Numbers of stoichiometric chiral auxilaries and catalytic methods have been developed to make chiral β-amino acids. One of the most promising processes for the convenient preparation of chiral β-amino acids on large scale is the asymmetric hydrogenation of suitable unsaturated precursors such as β-acetamido acrylates with Rh(I) catalysts bearing chiral phosphine ligands. The requisite prochiral substrates are easily available by treatment of β-keto carboxylates with NH4OAc and subsequent acylation. However, while literally thousands of reports are concerned with the Rh-catalyzed enantioselective hydrogenation of related prochiral α-acetamido acrylates, only a few devoted to the hydrogenation of β-analogues as substrates exist. The main reason for this is probably different behavior in the asymmetric hydrogenation, which had for a long time been attributed to particular substrates such as the isomeric ethyl 3-acetoamido butenoates (E)-1 and (Z)-1.

A Highly Efficient and Direct Approach for Synthesis of Enantiopure β‐Amino Alcohols by Reductive Cross‐Coupling of Chiral N‐tert‐Butanesulfinyl Imines with Aldehydes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of enantiopure azetidines: a route to new β-amino alcohols

β-Amino alcohols possessing an E vinylsilane moiety were cyclized in the presence of N-bromosuccinimide to afford diastereoisomerically pure polyfunctional azetidines. These azetidines were then transformed into enantiopure β-amino alcohols with a Z vinylic bromide moiety.

Enantioselective Hydrogenation of (E)-and (Z)-Isomeric Ethyl 3-Acetamidobutenoates with Rh-Bisphosphine Complexes: Effects of Substrate Geometry and Solvents on Reaction Rates and Catalyst Reusability

Enantiopure β-amino acids are crucial structural features of numerous biologically active natural products as well as important building blocks for the synthesis of β-peptides and β-lactam antibiotics. Numbers of stoichiometric chiral auxilaries and catalytic methods have been developed to make chiral β-amino acids. One of the most promising processes for the convenient preparation of chiral β-amino acids on large scale is the asymmetric hydrogenation of suitable unsaturated precursors such as β-acetamido acrylates with Rh(I) catalysts bearing chiral phosphine ligands. The requisite prochiral substrates are easily available by treatment of β-keto carboxylates with NH4OAc and subsequent acylation. However, while literally thousands of reports are concerned with the Rh-catalyzed enantioselective hydrogenation of related prochiral α-acetamido acrylates, only a few devoted to the hydrogenation of β-analogues as substrates exist. The main reason for this is probably different behavior in the asymmetric hydrogenation, which had for a long time been attributed to particular substrates such as the isomeric ethyl 3-acetoamido butenoates (E)-1 and (Z)-1.

A Highly Efficient and Direct Approach for Synthesis of Enantiopure β-Amino Alcohols by Reductive Cross-Coupling of Chiral N-tert-Butanesulfinyl Imines with Aldehydes

A highly efficient and practical approach for the synthesis of optically pure beta-amino alcohols by the SmI2-induced reductive cross-coupling of chiral N-tert-butanesulfinyl imines with aldehydes was developed. This method allows the preparation of a broad range of chiral beta-amino alcohols, including functionalized ones under mild conditions. It provides a straightforward access to enantiopure beta-amino alcohols that are widely applicable in asymmetric synthesis.

Synthesis of New Chiral Hydroxy Oxazolines and Their Use in the Catalytic Asymmetric Phenyl Transfer to Aldehydes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of new chiral hydroxy oxazolines and their use in the catalytic asymmetric phenyl transfer to aldehydes

Starting either from benzoylformic acid or ethyl oxamate and enantiopure β-amino alcohols, several chiral α-hydroxy oxazolines have been prepared by short synthetic routes. Subsequently, they have been employed in the catalytic asymmetric phenyl transfer to various aldehydes, using a mixture of triphenylborane and diethylzinc as the phenyl source. The corresponding secondary alcohols were obtained with good enantioselectivities (up to 81% ee) and up to 92% yield.

Advanced procedure for the enzymatic ring opening of unsaturated alicyclic β-lactams

Enantiopure β-amino acids 1a– 4a and β-lactams 1b– 4b were prepared simultaneously through the lipolase-catalysed enantioselective ring opening of unsaturated racemic β-lactams (±)- 1-(±)- 4. High enantioselectivities ( E>200) were observed when the reactions were performed with 1 equiv of water in iPr 2O at 70 °C. The resolved (1 R,2 S)-amino acids (yield⩾45%) and (1 S,5 R)-, (1 S,6 R)- and (1 S,8 R)-lactams (yield⩾47%) could be easily separated. The ring opening of lactam enantiomers 1b– 4b with 18% HCl afforded the corresponding β-amino acid hydrochlorides 1c·HCl– 4c·HCl (ee >95%).

Stereoselective Synthesis of β-Amino-α-Fluoro Esters via Diastereoselective Fluorination of Enantiopure β-Amino Enolates

β-Amino-α-fluoro esters have been prepared stereoselectively from t-butyl cinnamate and ethyl crotonate via tandem conjugate addition of lithium (S)-(-)-N-benzyl-N-α-methylbenzylamide, followed by fluorination with N-fluorobenzenesulfonimide. The ­absolute stereochemistry of the major diastereomers formed in each reaction was confirmed by X-ray crystallography. Complete deprotection to give (2S,3S)-α-fluoro-β-phenylalanine followed by Fmoc protection was achieved.

Highly Stereoselective Ring Expansion of Enantiopure α‐Hydroxyalkyl Azetidines.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Stereospecific Route to Enantiopure All cis-2,3,6-Trisubstituted Piperidines. Facile Synthesis of (-)-Deoxocassine and (+)-Azimic Acid.

For Abstract see ChemInform Abstract in Full Text.

Exploring Chiral Space en route to DPC 963: A Personal Account

AbstractFor Abstract see ChemInform Abstract in Full Text.